Large genomic aberrations detected by SNP array are independent prognosticators of a shorter time to first treatment in chronic lymphocytic leukemia patients with normal FISH

Ann Oncol. 2013 May;24(5):1378-84. doi: 10.1093/annonc/mds646. Epub 2013 Jan 31.

Abstract

Background: Genomic complexity can predict the clinical course of patients affected by chronic lymphocytic leukemia (CLL) with a normal FISH. However, large studies are still lacking. Here, we analyzed a large series of CLL patients and also carried out the so far largest comparison of FISH versus single-nucleotide polymorphism (SNP) array in this disease.

Patients and methods: SNP-array data were derived from a previously reported dataset.

Results: Seventy-seven of 329 CLL patients (23%) presented with a normal FISH. At least one large (>5 Mb) genomic aberration was detected by SNP array in 17 of 77 patients (22%); this finding significantly affected TTT. There was no correlation with the presence of TP53 mutations. In multivariate analysis, including age, Binet stage, IGHV genes mutational status and large genomic lesion, the latter three factors emerged as independent prognosticators. The concordance between FISH and SNP array varied between 84 and 97%, depending on the specific genomic locus investigated.

Conclusions: SNP array detected additional large genomic aberrations not covered by the standard FISH panel predicting the outcome of CLL patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Aberrations*
  • Female
  • Genotype
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • TP53 protein, human
  • Tumor Suppressor Protein p53